The host-parasite relationship in experimental and human syphilis will be examined, with particular emphasis on mechanisms of host resistance. Although numerous data have been collected concerning immune responses to syphilis infection, few conclusions can be reached regarding mechanisms of protection. The examination of T. pallidum-immunocyte interactions in experimental rabbit and human syphilis will be performed. The correlation of the presence of specifically sensitized lymphocytes with resistance to challenge will be examined in rabbits during the natural course of infection, following curative antibiotic therapy, and following administration of immune serum. Assays to be applied include serologic tests for syphilis (VDRL, FTA-ABS, and TPI), blastogenic responses to mitogens and T. pallidum antigens by unfractionated and purified T and B lymphocyte populations, and examination of T. pallidum presence as well as the T and B cell nature of the cellular infiltration in affected tissues. The in vitro interactions of sensitized lymphocytes and macrophages, separately and jointly, with virulent T. pallidum will be examined in human and experimental syphilis. Blastogenic responses of isolated human and rabbit lymphocytes (whole and fractionated populations) to T. pallidum antigens (Nichols and "street" strains) will be measured. It is anticipated that these studies will assist in the definition of immuologic responses to syphilis infection and will provide insights which may be useful in the development of effective immunization procedures.